Modern treatment methods led to a major improvement in the survival rate of children with Wilms' tumor. Combined therapy using surgery, radiation therapy, and chemotherapy has led to cure rates in excess of 85 percent. At the same time, it is recognized that all treatment forms have their risks and complications. Better understanding of the "natural history" of Wilms' tumor should lead to a refinement of the methods of management so as to achieve maximum survival with the least morbidity. The national yearly incidence of Wilms' tumor is estimated to be 450 in the United States. This frequency is too low for it to be feasible for even the largest pediatric institution to conduct purely intramural comparative trials. Groups of investigators interested in the Wilms' tumor problem therefore agreed to combine their efforts in a single investigation. Many institutions and researchers, both members of cooperative groups and those hitherto unaffiliated in such endeavors, have joined in this Study. The primary objectives of the first NWTS have now been achieved: (1) Routine post-operative radiation therapy is not essential in the treatment of all patients with localized tumors that are completely removed, (2) Treatment with both Actinomycin D and Vincristine is superior to the use of either agent alone. Study of the secondary objectives; namely, to obtain a better understanding of the tumor by studying gross and microscopic morphologic details, and "natural history" type information is still underway. NWTS-2 is built on the results of NWTS-1. The questions being addressed are the following: (1) Is fifteen months of maintenance AMD and VCR necessary to achieve the excellent results in GROUP I children reported in NWTS-1? (2) Will the addition of Adriamycin improve relapse-free survival and absolute survival rates when added to AMD and VCR?